HETEROMERIZATION OF G PROTEIN-COUPLED RECEPTORS: HOW MUCH DOES IT INFLUENCE THEIR BIOLOGICAL FUNCTION?

GIRONACCI MM

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2021; 2021

G protein-coupled receptors (GPCRs) are a remarkably multifaceted family of transmembrane proteins that exert a variety of physiological effects. They are targets for around one third of currently approved and clinical prescribed drugs and represent the largest and most structurally diverse family of transmembrane signaling proteins, with almost 1000 members identified in thehuman genome. Although GPCRs are able to operate as monomers, there is increasing evidence about the ability of GPCRs to form and function as heterodimers/heteromers that exhibit distinct pharmacological, trafficking and functional properties as compared to their parent monomeric or homodimeric/homomeric GPCRs. Efforts have focused over the past two decades on the identification of GPCR complexes as well as on their signaling properties. More recent findings have provided evidence for the existence of GPCR heteromerization in native tissues and animal models. In our lab we have been investigating how the functional properties of Mas receptor(R), a GPCR with protective actions that belongs to the renin-angiotensin system, are influenced by interaction with others GPCRs like the bradykinin type 2 (B2R) receptor, the dopamine type 2 receptor (D2R) and the Mrg-DR. MasR-B2R heteromerization influences MasR pharmacology,signaling and trafficking, while MasR-D2R heteromerization is necessary for MasR to display itsanti-inflammatory responses. GPCRs heteromerization not only brings forth a plethora of drug target combinations, but also gives an opportunity to carefully tweak the structure and function of one or more GPCRs involved in the complex, with the final goal of improving therapeutic strategies.